The present invention relates to a therapeutic agent for treating ulcerative colitis, which contains peony root. More particularly, the invention relates to a therapeutic agent for treating ulcerative colitis, having peony root or a Chinese medicine formulation containing peony root, which is very effective in repairing damaged tissues of ulcerative colitis and yet has no fear of side effects as those of steroids.
Ulcerative colitis is a diffuse nonspecific inflammatory disease that only causes inflammation mainly in large intestines, that is, the regions from the rectum to the intestinum cecum and is characterized by continuous lesion. The disease is characterized in that the region of inflammation is localized in mucosa and submucosa, remission and exacerbation are repeated, and it cannot be completely cured. From the characteristics, it is said that patients can be relatively easily diagnosed as ulcerative colitis.
With respect to the cause of ulcerative colitis, although there are various theories such as a theory that it is caused by food and life style and a theory that the cause is autoimmunity, the cause has not been convinced yet and the true cause is still unknown. Meanwhile, the enlargement process of inflammation of ulcerative colitis has been uncovered to a considerable extent and its knowledge has been disclosed in literatures, academic meetings, and the like. Ulcerative colitis cannot be treated by etiotropic therapy as a matter of fact and is treated by conservative therapy under the present conditions.
At present, drugs based on the knowledge of the uncovered enlargement process of the inflammation of ulcerative colitis are being actively developed. For example, clinical development tests of leukocyte removing therapy, lymphocyte removing therapy, anti-CD4 antibody, anti-TNF-xcex1 antibody and the like are being progressed.
In treatment of ulcerative colitis in actual clinical places, however, sulufasalazine (trade name: Salazopyrin) as a Sulfa drug or steroids which have been used for a long time is mainly administered. Treatment is given in which administration of the drugs, nutrition control, mental control, and the like are combined, and when it is still ineffective, surgical treatment is added. Such treatment is mainly given.
As for sulufasalazine and steroids used for drug therapy, sulufasalazine is relatively effective to patients with mild colitis and is used as a drug which is chosen first for the treatment of ulcerative colitis. The effect is, however, relatively weak on patients with severe colitis. Patients with mild colitis are often treated with both of sulufasalazine and steroids. In treatment in a remission phase of inflammation, in most cases, the combination of the drugs is switched to medication of only sulufasalazine. At an acute phase of inflammation, the medication of only sulufasalazine is often insufficient to produce an effect.
On the other hand, steroids often produce an excellent effect and are drugs mainly used in internal treatment. As its side effects have been known conventionally, it is necessary to be careful at the time of administration of steroids. It is also necessary to be very careful at the time of stopping the administration, what is called a withdrawal.
Although 5-ASA (5-aminosalicylate) which is considered to be an effective active part of sulufasalazine is clinically used, problems similar to those of sulufasalazine are also pointed out.
In view of the present conditions of treatment of ulcerative colitis, it is therefore an object of the invention to provide a therapeutic agent for treating ulcerative colitis, which is very effective in repairing tissues in an inflammatory region and yet exerts no side effects as those of steroids as a treatment agent based on the knowledge of the uncovered enlargement process of inflammation of ulcerative colitis.
Recently, a number of attempts to use Chinese herbal medicine to treat patients with ulcerative colitis are being made and a number of the following results have been published such as a case of enhancing anti-inflammatory power of, for example, steroids together with the medicine treatment (xe2x80x9cJournal of society of Japanese and Chinese medical treatmentxe2x80x9d Vol. 8, p516, 1991; and Japanese Unexamined Patent Application No. 6-40931), a case of obtaining mental stability (xe2x80x9cGendai Toyo Igaku (Modern oriental medicine)xe2x80x9d, Vol. 13, No. 1, p125, 1992), a case of improving constipation, diarrhea, and the like (xe2x80x9cGendai Toyo Igaku (Modern oriental medicine)xe2x80x9d, Vol. 12, No. 1, p115, 1991), and description of the direct effect of inflammation remission by administration of Ren-Shen-Tang (Ninjin-to) (xe2x80x9cNihon Toyo Igaku Zasshi (Magazine of Japan Oriental Medicine)xe2x80x9d, Vol. 42, No. 3, p337, 1992).
The inventors have paid attention to effects of treatment of ulcerative colitis by Chinese herbal medicine and have wholeheartedly studied. As a result, they have newly found that, among Chinese herbal medicine, peony root and Chinese medicine formulations containing peony root such as Jia-Wei-Xiao-Yao-San (Kami-shoyo-san), Dang-Gui-Shao-Yao-San (Toki-shakuyaku-san), Shao-Yao-Gan-Cao-Tang (Shakuyaku-kanzo-to), and Gui-Zhi-Fu-Ling-Wan (Keishi-bukuryo-gan) act on promotion of repairing tissues in an inflammatory region of ulcerative colitis and come to achieve the prevent invention.
In order to solve the problems, therefore, the invention provides a therapeutic agent for treating ulcerative colitis containing peony root as an active ingredient. As a specific embodiment, a therapeutic agent for treating ulcerative colitis containing dry powders of peony root as an active ingredient is provided.
As another embodiment of the present invention, it is provided a therapeutic agent for treating ulcerative colitis having a Chinese medicine formulation containing peony root as an active ingredient wherein, more particularly, the Chinese medicine formulation containing peony root is Jia-Wei-Xiao-Yao-San, Dang-Gui-Shao-Yao-San, Shao-Yao-Gan-Cao-Tan, or Gui-Zhi-Fu-Ling-Wan.
Peony root as an active ingredient of an ulcerative colitis treatment agent provided by the present invention may take forms of not only the peony root dry powders and the Chinese medicine formulation containing peony root as described above but also an infused dry extract of peony root or Chinese medicine formulation containing peony root.
As further embodiment of the present invention, it is provided a therapeutic agent for treating ulcerative colitis having, as an active ingredient, an infused dry extract of peony root, an infused dry extract of a Chinese medicine formulation containing peony root, or especially, an infused dry extract of Jia-Wei-Xiao-Yao-San, Dang-Gui-Shao-Yao-San, Shao-Yao-Gan-Cao-Tang, or Gui-Zhi-Fu-Ling-Wan.
Hitherto, Chinese medicine formulations play an auxiliary role in treatment of administrating sulufasalazine, steroids, and the like, that is, used only for the purpose of the effect which brings mental rest, the effect of suppressing diarrhea, and the like. Among Chinese medicine formulations, a formulation of the present invention containing, as an active ingredient, dry powders of peony root, an infused dry extract of peony root, or an infused dry extract of a Chinese medicine formulation containing peony root is very effective in repairing damaged tissues in ulcerative colitis as apparent from the results of tests which will be described hereinlater and yet has no fear of exerting side effects as those of steroids. The invention therefore can provide an excellent agent for treating ulcerative colitis.
Peony root (paeniae radix) as an active ingredient in the treatment agent provided by the present invention is obtained by drying the root of a perennial plant of the peony family (paeonia albiflora var. trichocarpa) grown in China, Korea, and Japan or a relative plant. Peony root is used as astringent, emollient, antispasmodic, analgesic, a drug for oversensitive to the cold, and a drug for dermatosis. Further, it is used for abdominal distension, abdominal pain, body pain, diarrhea, purulent tumor, and the like. Peony root is contained in Chinese medicine formulations such as Shao-Yao-Gan-Cao-Tang, Dang-Gui-Shao-Yao-San, Shi-Quan-Da-Bu-Tang (Juzen-taiho-to), Xiao-Qing-Long-Tang (Sho-seiryu-to), Da-Chai-Hu-Tang (Dai-saiko-to), Chai-Hu-Gui-Zhi-Tang (Saiko-keishi-to), Huang-Ling-Tang (Ogon-to), Si-Ni-San (Shigyaku-san), Dang-Gui-Jian-Zhong-Tang (Toki-kenvhu-to), Wen-Jing-Tang (Unkei-to), Zhen-Wu-Tang (Shimbu-to), Gui-Zhi-Shao-Yao-Zhi-Mu-Tang (Keishi-shakuyaku-chino-to), and the like.
The agent for treating ulcerative colitis provided by the present invention has, as an active ingredient, the dry powders of peony root or a Chinese medicine formulation containing peony root. Generally, a dose of 3 to 6 g of peony root is decocted and given per day. The infused dry extract of peony root can be prepared by, for example, a method of adding ten times (200 ml) of water to 20 g of finely chopped peony root, heating and refluxing the water and the chopped peony root for about three hours, filtering them, removing the residual material, and spray-drying the filtrate. It is preferable to administer the extract corresponding to 3 to 6 g per day as a dose of peony root.
As Chinese medicine formulations containing peony root, Jia-Wei-Xiao-Yao-San, Dang-Gui-Shao-Yao-San, Shao-Yao-Gan-Cao-Tang, Gui-Zhi-Fu-Ling-Wan, and the like can be mentioned.
Jia-Wei-Xiao-Yao-San is a formulation used for menopause symptom, menoxenia, autonomic imbalance, urethritis, chronic eczema, constipation, and the like and is prepared by, for example, 3.0 g each of Japanese angelica root, atractylodes rhizome, hoelen, and bupleurum root, 2.0 g each of glycyrrhiza, moutan bark, and gardenia fruit, and 1.0 g each of ginger and mentha herb. Generally, these crude drugs are administered in the form of either powders or decoction.
Dang-Gui-Shao-Yao-San is a formulation used for unidentified clinical syndrome, autonomic imbalance, menopause symptom, Meniere""s disease, hypotension, hypertension, endocrinosis, rhinitis, eczema, dysmenorrhea, endometritis, suffer from piles, proctoptosis, and the like. For example, it is prepared by 3.0 g each of Japanese angelica root, and cnidium rhizome and 4.0 g each of peony root, atractylodes rhizome, hoelen, and alisma rhizome. These crude drugs are administered in the form of either powders or decoction. At present, extract granules of the formulation are also prepared and sold.
Shao-Yao-Gan-Cao-Tang is a formulation used for abnormal tension of rectus abdominis muscles, abnormal tension and pain of striated smooth muscles, and various algetic diseases with crick of limb or the like. 3.0 g each of peony root and glycyrrhiza are put into 600 ml of water. The water with the crude drugs is boiled down to 300 ml and filtered. The filtrate is administered in the form of a hot drink three times a day.
Gui-Zhi-Fu-Ling-Wan is a formulation used for various disorders caused by menoxenia, menopause symptom, neuronosis, neurosis, depression, eczema, urticaria, hemorrhoids, orchitis, and the like. Cinnamon fuigs, hoelen, moutan bark, peach kernel, and peony root are powdered, kneaded with honey, and pilled. Alternately, 4.0 g each of the above crude drugs are put into 600 ml of water. The water with the crude drugs is boiled down to 300 ml and filtered. The filtrate is administered in the form of a hot drink two or three times a day.
The agent for treating ulcerative colitis provided by the invention can take the forms of powders, granules, pills, tablets, capsules, and decoctions of trade drugs on the basis of any of the Chinese medicine formulations. When considering easiness of taking medicine, easiness of formulation, portability, and the like, a dry extract of a Chinese herbal medicine can be used as it is. Powders, granules, pills, fine granules, tablets, capsules, decoctions and the like obtained by processing the extract are preferably used.
A method of preparing an infused dry extract of any of the above-mentioned Chinese medicine formulations will be described with respect to the case of gui-zhi-fu-ling-wan as an example. The crude drugs according to the formulation and 600 ml of water are boiled down to 300 ml. The filtrate liquid is dried by a proper method such as spray dry or freezed dry. Powders of the extract of gui-zhi-fu-ling-wan are accordingly obtained, which may be used as they are as a Chinese extract.
Meanwhile, when the extract powders are processed into other forms, formulations in powders, granules, fine granules, pills, tablets, capsules, decoctions and the like can be prepared in accordance with a usual formulation preparing method by properly adding the following agents used for ordinary formulation: an excipient such as lactose, corn starch, or crystalline cellulose; a lubricant such as talc, magnesium stearate, or sucrose fatty acid ester; further, as necessary, a fluidity accelerator such as light anhydrous silicic acid or synthetic aluminum silicate; a disintegrator such as starch, hydroxypropyl starch, or carboxymethylcellulose calcium; a binder such as dextrin, acacua, methylcellulose, hydroxypropylcellulose, or polyvinyl pyrrolidone; a surfactant such as sodium lauryl sulfate, or polysorbate 80.
In case of compounding two or more kinds of Chinese herbal medicine extracts, the extracts may be prepared separately and compounded. Alternately, a formulation may be also prepared according to an usual method by compounding powders of respective extracts and adding excipient, lubricant, fluidity accelerator, disintegrator, binder, surfactant, and the like to the powders.